At mepopause most women lose their gepder-related biological protection and develop symptoms that adversely affect their lives, e.g., hypertension, stroke and insulin resistance. The loss of estrogen appears to be central to the deleterious effects, but recent findings strongly discourage the use of hormone replacement therapy. A growing number of women have turned to dietary supplements to alleviate these effects, but their efficacy and safety are largely untested. In female ovariectomized spontaneously hypertensive stroke prone rats, three botanical extracts (e.g., genistein, kudzu and grape seed extract) can jpdependently blunt hypertension and decrease cognitive decline. In this model resistance vessels are compromised by the loss of estrogen, and these effects are significantly blunted by dietary polyphenols. Determining the mechanism of action of these botanicals has been difficult, because the polyphenols are typically metabolized rapidly, and therefore, their distribution into body compartments is not easily followed. However, our preliminary data suggest that the primary polyphenol in kudzu root, i.e., puerarin, is transported to body compartmepts ip a rapid and unmetabolized state, and thus, its distribution can be readily traced. This suggests that kudzu polyphenols may provide a useful tool to uncover mechanisms by which polyphenols protect against diseases. These studies will elucidate the mechanism(s) by which kudzu root blunts the cascades leading to hypertension, endothelial dysfunction and cognitive loss in this model and compare these mechanisms to those underlying similar effects of the major soy polyphenol, i.e., genistein. These studies will elucidate the bioavailability, safety, efficacy, mechanisms and protein interactions that underlie the beneficial actions. Previous studies used a narrow approach that examined only one or two dimensions of the effects of botanicals, but we propose a multidisciplinary approach, which will elucidate a broad range of the health benefits/risks of botanical treatments.